Review
Multidisciplinary Sciences
Erika Wakayama, Taiki Kuzu, Keisuke Tachibana, Ryuichi Hirayama, Yoshiaki Okada, Masuo Kondoh
Summary: The blood-brain barrier poses a challenge to drug delivery to the central nervous system. Among the components of the tight junctions in the blood-brain barrier, claudin-5 has been studied extensively as a target for enhancing drug permeation into the brain. However, sustained knockdown of claudin-5 is lethal in mice and administration of an anti-claudin-5 antibody can cause convulsions in nonhuman primates.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)
Review
Cell Biology
Hideki Chiba, Naoki Ichikawa-Tomikawa, Tetsuya Imura, Kotaro Sugimoto
Summary: The neurovascular unit (NVU) is a complex structure consisting of different types of cells, with microvascular endothelial cells and pericytes playing a crucial role in maintaining the blood-brain barrier (BBB). CLDN5, the most abundantly expressed tight-junction protein in brain microvascular endothelial cells, is essential for BBB integrity and its regional dysregulation may contribute to CNS disorders. The link between cell adhesion and transcription factor signalings, particularly involving CLDN5-adhesion signaling, is explored as a potential mechanism in brain health and disorders.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jong-Chan Ahn, Su Jung Hwang, Hyo-Jong Lee, Kyu-Won Kim
Summary: The study showed that claudin-5a is crucial for establishing and maintaining the blood-neural barrier during zebrafish development. Knockdown of claudin-5a resulted in selective leakage through the BBB, decreased expression of glucose transporter 1 in cerebral microvessels, and leakiness in the blood-cerebrospinal fluid barrier, indicating overall abnormal development of the blood-neural barriers.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
(2021)
Article
Clinical Neurology
Yosuke Hashimoto, Karine Poirier, Nathalie Boddaert, Laurence Hubert, Melodie Aubart, Anna Kaminska, Marianne Alison, Isabelle Desguerre, Arnold Munnich, Matthew Campbell
Summary: This study reports a novel mutation in the CLDN5 gene associated with alternating hemiplegia with microcephaly. The mutation leads to the conversion of the blood-brain barrier into an anion-selective channel, indicating that CLDN5 associated alternating hemiplegia is a channelopathy.
Review
Biochemistry & Molecular Biology
Arseniy E. Yuzhalin, Dihua Yu
Summary: This review provides an overview of the role of extracellular matrix (ECM) in brain metastasis. It discusses the involvement of ECM in disrupting the blood-brain barrier, modulating brain metastasis dormancy, regulating brain metastasis seeding through activated integrin signaling, and the functions of brain-specific ECM protein reelin in brain metastasis. The possibility of targeting ECM for brain metastasis management is also considered.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Neurosciences
Elisabeth Pellegrini, Danielle Fernezelian, Cassandra Malleret, Marie-Madeleine Gueguen, Jessica Patche-Firmin, Sepand Rastegar, Olivier Meilhac, Nicolas Diotel
Summary: The blood-brain barrier plays a key role in maintaining brain homeostasis and can be regulated by estrogens. In zebrafish, estrogens have a strong synthesizing activity due to the expression of Aromatase B protein in radial glial cells. Estrogen treatment in zebrafish increases the expression of tight junction and claudin 5 genes in adult males, but has no impact in females. The intimate links between endothelial cells and neural stem cells suggest a potential mechanism for the uptake of peripheral steroids and their role in modulating neurogenic activity.
JOURNAL OF COMPARATIVE NEUROLOGY
(2023)
Article
Pharmacology & Pharmacy
Junzhi Yang, Robert D. Betterton, Erica Williams, Joshua A. Stanton, Elizabeth S. Reddell, Chidinma E. Ogbonnaya, Emma Dorn, Thomas P. Davis, Jeffrey J. Lochhead, Patrick T. Ronaldson
Summary: The consumption of acetaminophen (APAP) can induce neurological changes in human subjects, but its effects on blood-brain barrier (BBB) integrity are still unclear. Changes in BBB by APAP can have significant consequences for the delivery of co-administered drugs to the brain. The study found that high doses of APAP can increase BBB permeability. These findings are important for patients who abuse or misuse APAP and opioid drugs.
Article
Biotechnology & Applied Microbiology
Yiyang Li, Bowen Liu, Tingting Zhao, Xingping Quan, Yan Han, Yaxin Cheng, Yanling Chen, Xu Shen, Ying Zheng, Yonghua Zhao
Summary: This study compared the protective efficacy of bone marrow mesenchymal stem cells derived extracellular vesicles (BMSC-EVs) and brain endothelial cells derived extracellular vesicles (BEC-EVs) on blood-brain barrier (BBB) integrity after acute ischemic stroke (IS). The findings indicated that both types of EVs had similar protective effects on reducing cerebral infarction volume, BBB leakage, and enhancing the expression of tight junction proteins ZO-1 and Claudin-5. Furthermore, BMSC-EVs showed superior efficacy in suppressing Caveolin-1 and improving neurological function.
JOURNAL OF NANOBIOTECHNOLOGY
(2023)
Article
Neurosciences
Yanyu Li, Chunchun Wang, Liang Zhang, Bing Chen, Yuqian Mo, Jingjing Zhang
Summary: This study investigated the roles of Claudin-5a and -5b in the formation and maintenance of blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) in zebrafish. The results showed that Claudin-5a and -5b are both expressed in zebrafish cerebrovascular endothelial cells (ECs), but only Claudin-5a has a significant impact on the development and function of both BBB and BCSFB.
FLUIDS AND BARRIERS OF THE CNS
(2022)
Article
Biochemistry & Molecular Biology
Kotaro Sugimoto, Naoki Ichikawa-Tomikawa, Keisuke Nishiura, Yasuto Kunii, Yasuteru Sano, Fumitaka Shimizu, Akiyoshi Kakita, Takashi Kanda, Tetsuya Imura, Hideki Chiba
Summary: Our research found that 5-HT1A receptors are expressed in brain microvascular endothelial cells and mural cells in the normal prefrontal cortex, and that PKA is aberrantly activated in both cell types in the schizophrenic PFC. Additionally, serotonin/5-HT1A signaling enhances endothelial CLDN5 expression in BMVECs under two-dimensional co-culture conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Zhenguo Yang, Panpan Lin, Bing Chen, Xiaoqi Zhang, Wei Xiao, Shuilong Wu, Chunnian Huang, Du Feng, Wenqing Zhang, Jingjing Zhang
Summary: In stroke patients, autophagy activation leads to abnormal aggregation of CLDN5 in BMECs, causing BBB breakdown. Meanwhile, autophagy also contributes to the degradation of CAV1 and aggregated CLDN5, alleviating BBB impairment.
Article
Cell Biology
Monica Diaz-Coranguez, Laura Gonzalez-Gonzalez, Amy Wang, Xuwen Liu, David A. Antonetti
Summary: This study reveals the involvement of DVL1 in norrin-induced blood-retinal barrier restoration. DVL1 promotes tight junction stabilization through a non-canonical signaling pathway involving direct binding to CLDN5.
Article
Biology
Esther Sasson, Shira Anzi, Batia Bell, Oren Yakovian, Meshi Zorsky, Urban Deutsch, Britta Engelhardt, Eilon Sherman, Gad Vatine, Ron Dzikowski, Ayal Ben-Zvi
Summary: Through super-resolution microscopy, new structural and functional properties of BBB TJs were revealed, showing a compacting arrangement of claudin-5 proteins during mouse development. The clustering of ZO1 was found to be independent of claudin-5 in vivo, and contrary to previous knowledge, total levels of claudin-5 were inversely correlated with TJ functionality in the developmental context.
Article
Engineering, Environmental
Zengjin Wang, Congcong Zhang, Fengyan Huang, Xiaojing Liu, Zhiping Wang, Bing Yan
Summary: Ingestion of nanoparticles during pregnancy can be dangerous to fetal brain development, especially in early pregnancy. Experimental results show that nanoparticles can cross multiple biological barriers, and the toxicity to the fetus depends on the stages of pregnancy and fetal development.
JOURNAL OF HAZARDOUS MATERIALS
(2021)
Review
Biochemistry & Molecular Biology
Rina Fujiwara-Tani, Shiori Mori, Ruiko Ogata, Rika Sasaki, Ayaka Ikemoto, Shingo Kishi, Masuo Kondoh, Hiroki Kuniyasu
Summary: CLDN4 is a crucial component of tight junctions in epithelial cells and is overexpressed in many epithelial malignancies. Changes in CLDN4 expression are associated with epigenetic factors, inflammation, and growth factor signaling. CLDN4 plays a role in maintaining the tumor microenvironment and acts as a barrier to anticancer drug entry.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Etienne Atangana, Ulf C. Schneider, Kinga Blecharz, Salima Magrini, Josephin Wagner, Melina Nieminen-Kelha, Irina Kremenetskaia, Frank L. Heppner, Britta Engelhardt, Peter Vajkoczy
TRANSLATIONAL STROKE RESEARCH
(2017)
Review
Clinical Neurology
Jean-Francois Ghersi-Egea, Nathalie Strazielle, Martin Catala, Violeta Silva-Vargas, Fiona Doetsch, Britta Engelhardt
ACTA NEUROPATHOLOGICA
(2018)
Editorial Material
Clinical Neurology
Britta Engelhardt
ACTA NEUROPATHOLOGICA
(2018)
Article
Endocrinology & Metabolism
Stephanie Uster, Fernanda Matos Coelho, Daniel Aeberli, Jens V. Stein, Wilhelm Hofstetter, Britta Engelhardt, Michael Seitz
Article
Immunology
Silvia Tietz, Therese Perinat, Gretchen Greene, Gaby Enzmann, Urban Deutsch, Ralf Adams, Beat Imhof, Michel Aurrand-Lions, Britta Engelhardt
BRAIN BEHAVIOR AND IMMUNITY
(2018)
Letter
Neurosciences
Maria Eleftheria Evangelopoulos, Andrei Miclea, Lisa Schrewe, Myriam Briner, Anke Salmen, Britta Engelhardt, Andrea Huwiler, Andrew Chan, Robert Hoepner
CNS NEUROSCIENCE & THERAPEUTICS
(2018)
Article
Cell Biology
Stefan Roth, Vikramjeet Singh, Steffen Tiedt, Lisa Schindler, Georg Huber, Arie Geerlof, Daniel J. Antoine, Antoine Anfray, Cyrille Orset, Maxime Gauberti, Antoine Fournier, Lesca M. Holdt, Helena Erlandsson Harris, Britta Engelhardt, Marco E. Bianchi, Denis Vivien, Christof Haffner, Juergen Bernhagen, Martin Dichgans, Arthur Liesz
SCIENCE TRANSLATIONAL MEDICINE
(2018)
Article
Biochemistry & Molecular Biology
Gaby Enzmann, Roberto Adelfio, Aurelie Godel, Neda Haghayegh Jahromi, Silvia Tietz, Sabrina S. Burgener, Urban Deutsch, Hartmut Wekerle, Charaf Benarafa, Britta Engelhardt
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Neurosciences
Mariana Castro Dias, Caroline Coisne, Pascale Baden, Gaby Enzmann, Lillian Garrett, Lore Becker, Sabine M. Hoelter, Martin Hrabe de Angelis, Urban Deutsch, Britta Engelhardt, Antonio Aguilar-Pimentel, Thure Adler, Dirk H. Busch, Nadine Spielmann, Kristin Moreth, Wolfgang Hans, Oana Amarie, Jochen Graw, Jan Rozman, Ildiko Radc, Frauke Neff, Julia Calzada-Wack, Birgit Rathkolb, Eckhard Wolf, Thomas Klopstock, Wolfgang Wurst, Johannes Beckers, Manuela Oestereicher, Gregor Miller, Holger Maier, Claudia Stoeger, Stefanie Leuchtenberger, Valerie Gailus-Durner, Helmut Fuchs
FLUIDS AND BARRIERS OF THE CNS
(2019)
Review
Biochemistry & Molecular Biology
Mariana Castro Dias, Josephine A. Mapunda, Mykhailo Vladymyrov, Britta Engelhardt
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Medicine, Research & Experimental
Zhilin Li, Emilia A. Korhonen, Arianna Merlini, Judith Strauss, Eleonoora Wihuri, Harri Nurmi, Salli Antila, Jennifer Paech, Urban Deutsch, Britta Engelhardt, Sudhakar Chintharlapalli, Gou Young Koh, Alexander Fluegel, Kari Alitalo
JOURNAL OF CLINICAL INVESTIGATION
(2020)
Review
Neurosciences
David M. F. Francisco, Luca Marchetti, Sabela Rodriguez-Lorenzo, Eduardo Frias-Anaya, Ricardo M. Figueiredo, Peter Winter, Ignacio Andres Romero, Helga E. de Vries, Britta Engelhardt, Remy Bruggmann
FLUIDS AND BARRIERS OF THE CNS
(2020)
Article
Medicine, General & Internal
Steven T. Proulx, Britta Engelhardt
Summary: The central nervous system maintains a unique relationship with the immune system through brain barriers, allowing for immune surveillance and protection of neural tissue without activating immune responses unless direct injury occurs.
JOURNAL OF INTERNAL MEDICINE
(2022)
Meeting Abstract
Surgery
F. Baier, F. Jebbawi, A. Keogh, D. Sanchez, R. Kudira, G. Loforese, M. Furuse, M. Castro Dias, U. Deutsch, B. Engelhardt, G. Beldi, D. Candinas, D. Stroka
BRITISH JOURNAL OF SURGERY
(2018)
Meeting Abstract
Physiology
G. Enzmann, M. Vaas, S. Pavlidou, J. Klohs, B. Engelhardt
JOURNAL OF VASCULAR RESEARCH
(2017)
